Mutations and response to epidermal growth factor receptor inhibitors.

Abstract

Novel therapeutic agents targeting the epidermal growth factor receptor (EGFR) have improved outcomes for a subgroup of patients with colorectal, lung, head and neck, and pancreatic cancers. In these tumors, the EGFR activation turns on at least five different signaling pathways (RAS/mitogen-activated protein kinase, phospholipase C, phosphatidylinositol 3-kinase/AKT, signal transducer and activator of transcription, and SRC/FAK pathways), which are intimately interconnected, and frequent mutations involving either the receptor itself or downstream effectors have been found. Up to now, it seems that alterations at the EGFR level has major importance in EGFR tyrosine kinase inhibitor response, whereas modifications of downstream effectors could lead to treatment resistance. Furthermore, our understanding of the mechanism of the EGFR network activation provides new hypotheses on potential new anticancer drugs that may be effective.

• Authors: Pierre Laurent-Puig, Astrid Lievre, Hélène Blons
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 15 Issue 4 Pg. 1133-9 (Feb 15 2009) ISSN: 1078-0432 [Print] United States
• PMID: 19228718 (Publication Type: Journal Article, Review)

Chemical References

• Protein Kinase Inhibitors
• Phosphatidylinositol 3-Kinases
• ErbB Receptors
• Proto-Oncogene Proteins c-akt
• PTEN Phosphohydrolase

Topics

• Animals
• ErbB Receptors (antagonists & inhibitors, genetics)
• Gene Amplification
• Genes, ras
• Humans
• MAP Kinase Signaling System
• Mutation
• Neoplasms (drug therapy, genetics)
• PTEN Phosphohydrolase (physiology)
• Phosphatidylinositol 3-Kinases (genetics)
• Protein Kinase Inhibitors (therapeutic use)
• Proto-Oncogene Proteins c-akt (genetics)